RT Journal Article SR Electronic T1 CD40 Ligand and CTLA-4 Are Reciprocally Regulated in the Th1 Cell Proliferative Response Sustained by CD8+ Dendritic Cells JF The Journal of Immunology JO J. Immunol. FD American Association of Immunologists SP 1182 OP 1188 DO 10.4049/jimmunol.169.3.1182 VO 169 IS 3 A1 Fallarino, Francesca A1 Grohmann, Ursula A1 Vacca, Carmine A1 Bianchi, Roberta A1 Fioretti, Maria C. A1 Puccetti, Paolo YR 2002 UL http://www.jimmunol.org/content/169/3/1182.abstract AB Subsets of murine dendritic cells (DCs) from the spleen differ in their ability to induce proliferative responses in both primary and secondary CD4+ T cells. Recent evidence indicates that lymphoid-related CD8+ DCs fail to provide appropriate signals to freshly isolated secondary CD4+ T cells to sustain their proliferation in vitro. In the present study, we examined peptide-pulsed CD8− and CD8+ DCs for ability to stimulate Th1 and Th2 cell clones with the same Ag specificity. Defective ability to induce proliferation was selectively shown by CD8+ DCs presenting Ag to the Th1 clone. The deficiency in CD8+ DCs was overcome by CD40 triggering before peptide pulsing. When exposed to CD8+ DCs in the absence of CD40 activation, the Th1 clone expressed low levels of CD40 ligand and high levels of surface CTLA-4. Neutralization of CTLA-4 during the DC/T cell coculture resulted in increased CD40 ligand expression and proliferation of T cells. Remarkably, the activation of CD40 on DCs under conditions that would increase Th1 cell proliferation, also resulted in down-regulation of surface CTLA-4. These results confirm differential effects of CD8+ and CD8− DCs in the stimulation of Ag-primed Th cells. In addition, they suggest that reciprocal regulation of CD40 ligand and CTLA-4 expression occurs in Th1 cells exposed to CD8+ DCs.